Compositions incorporating (-)-hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors

ABSTRACT

Methods for promoting healthy body weight and improving a variety of related physiological factors, including serum serotonin levels, serum leptin levels, fat oxidation, cholesterol levels, and body mass index, in persons or other mammals, include administering to those persons or other mammals effective amounts of hydroxycitric acid or a combination of hydroxycitric acid, chromium and gymnemic acid, which work synergistically to further to promote healthy body weight and improve these physiological factors.

This application claims the benefit of U.S. Provisional PatentApplication Ser. No. 60/343,473, filed Dec. 20, 2001.

The present invention relates generally to compositions and relatedmethods for promoting healthy body weight, including reducing excessbody weight or maintaining healthy body weight, and improving relatedhealth factors, such as cholesterol levels and body mass index, inpersons and other mammals.

Excess body weight is becoming more prevalent worldwide at an alarmingrate, both in developing and developed countries. Approximately 61percent of adults in the U.S. are overweight (i.e., having a body massindex (BMI) of greater than 25 kg/m²), while more than 26 percent ofU.S. adults are obese (i.e., having a BMI of greater than 30 kg/m²).Obesity is the second leading cause of premature death in the U.S.Approximately 300,000 Americans die each year from complications causedby obesity. According to the World Health Organization, there are over300 million obese adults worldwide. Environmental and behavioral changesbrought about by economic development, modernization and urbanizationhave been linked to the global rise in obesity in adults and children,the true health consequences of which may not be fully known for yearsto come. Consumption of western-style diets, low levels of physicalactivity and sedentary lifestyles generally have been implicated in theworldwide trend of weight gain.

Increase in body weight results from an imbalance between energy intakeand expenditure in a person, manifested by excessive expansion ofadipose tissue mass in the person. Obesity leads to a number of poorhealth factors. In particular, obesity increases the risk of high bloodpressure, hypertension, type II diabetes, arthritis, elevatedcholesterol, and cancer. Although 30-40% of obese people claim they aretrying to lose or maintain body weight, their success rate is low.Dietary approaches for the management of excess body weight have beenunsuccessful due to improper caloric restriction and/or lack of physicalexercise. Low calorie diets can provide for temporary weight loss, butthey have not proven themselves as long-term solutions for people tryingto lose or maintain weight. Drugs that suppress appetite, reduce foodintake, increase energy expenditure and/or affect nutrient partitioningor metabolism have potential efficacy in reducing body weight.Unfortunately, these also frequently are accompanied by adverse sideeffects, some of which are life threatening.

High blood cholesterol, high blood triglyceride levels, and obesity allare indicators of increased risk for heart disease and other healthmaladies. In particular, high levels of total cholesterol, LDLcholesterol or triglycerides, as well as low levels of HDL cholesterol,all are risk factors for various cardiovascular diseases. Theseconditions are exacerbated by many factors, including poor diet, lack ofexercise and obesity. Prevalence for obesity can be reflected inexcessive eating and also by genetic factors. One method for reducingappetite, and therefore excessive eating, is by raising serotonin levelsin a person. Increased brain levels of serotonin, an importantneurotransmitter involved in proper brain function, including regulationof sleep and mood, have also been linked with appetite suppression.Also, a known biomarker for genetic propensity of a person towardobesity is serum leptin, a hormone encoded by the gene that regulatesbody weight. Leptin binds to receptors in the brain, where it activatessignals that inhibit food intake and increase energy expenditure.Studies have shown that plasma leptin levels are higher in overweightthan in non-overweight individuals, and higher in women than in men.

The methods described above to treat obesity in humans may be applicableto treating other mammals as well, including animals commonly kept aspets, such as dogs and cats. Excess body weight has reached epidemicproportions in, and is the most common nutritional disorder among, pets.It is estimated that 50% of pets (or roughly 60 million animals) in theUnited States are overweight or obese (a weight ten percent over idealbody weight is considered overweight, and a weight twenty percent overideal body weight is clinically defined as obese). An extra five poundson a dog that should weigh 17 pounds or an extra three pounds on a catthat should weight 10 pounds is comparable to an extra 50 pounds on aperson who should weigh 170 pounds. Overweight pets are at higher riskof developing health problems such as heart disease, skeletal problems,breathing problems, diabetes and arthritis. Traditionally, weightmanagement in veterinary medicine relies on one or more recommendations.A veterinarian may prescribe high fiber/reduced calorie diets, oradvocate other dietary changes focusing on a decrease in overall caloricintake. Another method to manage pet weight is to increase exercise.Untreated obesity can be a devastating condition for a pet, andinstituting an obesity-management program will add quality years to apet's life.

Various methods exist for treating obesity and the other related healthfactors discussed above, such as improved diet, increased exercise, andvarious medications. These, however, have not been entirely effectivetreatments. Diet modification and increased exercise can be difficultfor some individuals to maintain for an extended period, and medicationsintroduce the possibility of negative side effects.

One dietary supplement known for promoting weight loss is(−)-hydroxycitric acid (HCA). HCA is an organic acid similar to citricacid that is found in citrus fruits, such as oranges and lemons, butthat has remarkably different properties from citric acid. HCA has beenshown to reduce appetite, inhibit fat synthesis, and decrease bodyweight in persons consuming it, without stimulating the central nervoussystem of those persons. Therefore, ingestion of HCA will not causenervousness, rapid heart rate, high blood pressure, or insomniaassociated with dietary stimulants such as ephedra (Ma-Huang), caffeineor phenylpropanolamine. Furthermore, in acute toxicity tests, HCA hasbeen show to be even safer than citric acid. HCA predominantly ispresent in the fruit rind of plants in the genus Garcinia, such asGarcinia cambogia (of the family Guttiferae), a tree native to South andSoutheast Asia. The dried fruit rind, also known as Malabar Tamarind, isextensively used in Southern India for culinary purposes. The fruitexhibits a distinctive sour taste and has been used for centuries tomake meals more “filling.”

HCA has been sold as a dietary supplement since 1994, but research onHCA and its effects stretches back over 30 years. In 1969, researchersdemonstrated that HCA is a competitive inhibitor of A TP-citrate lyase,the enzyme responsible for catalyzing the extramitochondrial cleavage ofcitrate to oxaloacetate and acetyl-CoA, a building block of fatty acidsynthesis. A TP-citrate lyase is important in maintaining the acetyl-CoApool for fatty acid and cholesterol biosynthesis, particularly duringthe hyperlipogenic nutritional state produced by high carbohydratefeeding. HCA has been shown to be a highly effective inhibitor of fattyacid synthesis by rat liver in vivo. HCA is theorized to reduce foodconsumption in humans by diverting carbohydrates away from fat synthesisand towards the synthesis of stored energy in the form of glycogen.Increased glycogen levels in the liver and muscles are believed to senda satiety signal to the brain that the body is “full,” resulting inreduced appetite and food intake.

Another possible mechanism of action may be HCA's ability to stimulateserotonin release and inhibit its reuptake in the body. Serotonin(5-HT), a vital neurotransmitter, is involved in a wide range ofbehavioral functions in the body, including mood, sleep and appetitecontrol. Studies have shown that serotonin affects eating behavior andbody weight. Increased plasma levels of serotonin are associated withdecreased food intake, reduced weight gain and increased energyexpenditure. Another benefit of increasing serotonin levels in the bodymay be in addressing many of the emotional issues overweight peopleface, including binge eating and depression. It is well established thatserotonin and peptides such as neuropeptide Y are involved in theregulation of eating behavior. It is not certain that HCA's ability tocurb appetite and reduce food intake derives from these mechanisms.However, as stated above, HCA produces its effects without stimulatingthe central nervous system, avoiding the related disadvantages of this.

Another possible mechanism of action may be HCA's ability todown-regulate the obesity regulatory gene as determined by serum leptinlevels. Leptin is a 167 amino acid protein hormone encoded by the genethat regulates body weight. Synthesized and secreted by adipocytes (fatcells), leptin binds to receptors in the brain, where it activatessignals that inhibit food intake and increase energy expenditure. Whenreceptor-binding activity is diminished, a condition called “leptinresistance,” plasma leptin levels increase and the leptin loses itsability to inhibit food intake and increase energy expenditure. Asstated previously, studies show that plasma leptin levels are higher inoverweight than in non-overweight individuals, and higher in women thanin men. Leptin is synthesized and secreted by adipocytes, is present inthe bloodstream in amounts related to the amount of fat in the body, andacts primarily on the brain to regulate food intake. Leptin has beenshown to be able to modulate insulin secretion and action through thesereceptors. These findings confirm earlier observations of higher leptinlevels in obese individuals than in lean individuals.

Another possible mechanism of action may be HCA's ability to increasefat oxidation. Fat metabolites are products of fat degradation.Following exercise or other fat “burning” processes, fat tissue breaksdown into small molecular components, including malondialdehyde,formaldehyde, acetaldehyde and acetone. Increased urinary levels of fatmetabolites indicates increased fat degradation or “burning.” While themajority of studies on HCA have focused on its mechanism of action atthe metabolic level, until recently, no studies have investigated itseffect on neurotransmitters associated with the control of appetite,hormones associated with the regulation of body weight, nor fatoxidation. Recent studies on the effect of HCA on serum serotoninlevels, serum leptin levels, and fat oxidation, are discussed below.

The potential of HCA as an inhibitor of lipogenesis has been examined,and it was demonstrated that HCA curbs appetite, reduces food intake andinhibits fat synthesis. Oral administration of HCA has been shown tosignificantly depress in vivo lipogenic rates in a dose-dependent mannerin the liver, adipose tissue and small intestine. This hepaticinhibition has been shown to be significant for the 8-hour period whencontrol animals demonstrated elevated rates of lipid synthesis. Thekinetics of in vivo hepatic lipogenesis reduction were identical afteracute or chronic administration of HCA. However, in relevant studiesrates of lipogenesis were depressed after chronic administration of HCAfor 30 days, thus HCA may help prevent “fat rebound,” a commonoccurrence where most diets fail, resulting in fat regain once the dietis discontinued. Rats receiving HCA consumed less food than theuntreated controls, but this decreased caloric intake was notresponsible for the drug-induced depression of hepatic lipogenesis, asshown by studies using pair fed rats. In these studies, an acute oraldose of HCA (2.63 mmoles/kg equivalent to roughly 594 mg/kg body weight)given prior to a standardized synthetic meal caused a significantdecrease in liver lipogenesis (roughly 70%) for up to 8 hours after themeal. The production of lipids declined not only in the liver, but inthe other tissues in which fats are formed from carbohydrates (i.e.,small intestine and adipose tissues).

In one experiment, rats were given various amounts of HCA over a thirtyday period (in amounts of 2.63, 1.32, 0.66 or 0.17 mmoles/kg/day) oncedaily, or 0.33 moles/kg twice daily, to demonstrate the effect on bodyweight gain in growing rats. A dose-related reduction in weight gain wasobserved in the rats treated with HCA. The decreases were significant atconcentrations of 2.63 mmoles/kg once daily or 0.33 mmoles/kg twicedaily. Thus, one-fourth the amount of HCA was required to reduce weightgain when administered in two divided doses as compared to a singledose. However, no significant reductions were observed with the singledaily administration of 0.17, 0.66 and 1.32 nmoles/kg. This suggeststhat HCA is rapidly metabolized in the body and that divided doses aremore effective than a single dose at inhibiting lipogenesis. Recentstudies also have shown that HCA-induced increases in energy expendituremay account, at least in part, for the observed inhibitory effect of HCAon body weight gain in rats.

A particularly preferred HCA composition, marketed under the name SuperCitriMax® (and also designated HCA-SX) by InterHealth Nutraceuticals ofBenicia, Calif., incorporates a unique form of HCA bound to the mineralscalcium and potassium. HCA-SX is described and claimed in publishedPatent Cooperation Treaty Application WO 99/03464, herein incorporatedby reference. This HCA-SX composition contains approximately 60% byweight of HCA, 11% by weight of calcium and 16% by weight of potassium,with the remaining 13% consisting of water and other naturally occurringconstituents of the natural Garcinia fruit rind. This is in contrast toother, more common forms of HCA, which are not bound to potassium, butinstead are bound only to calcium. As a result of being bound also topotassium, HCA-SX is virtually completely water-soluble, and it is morebioavailable than regular HCA compositions incorporating only calcium.HCA-SX is also significantly less hygroscopic than HCA compositionsbound only to potassium, contains 60% HCA—twenty percent more HCA thanthat typically found in HCA compositions geared toward weight loss—andcontains less than one percent sodium, which is of particular benefit topeople who have high blood pressure or are on a sodium-restricted diet.HCA-SX also is virtually tasteless, odorless and, in solution,colorless, and does not have the aftertaste associated with other HCAcompositions, making it ideal for use in functional foods and beverages.

As stated above, HCA-SX is highly bioavailable and easily retained byobese subjects. Using a new rapid and accurate gas chromatography/massspectrometric method for measuring blood levels of HCA, scientistsrecently found that blood levels of HCA-SX increased for at least 2hours and remained in the blood for more than 4 hours after ingestion.Absorption rates varied among subjects. In a separate experiment, thesame investigators found that absorption of HCA-SX peaked two hoursafter administration, and that the compound remained in the blood formore than nine hours after ingestion. Eating a full meal shortly aftertaking HCA-SX reduced its absorption by about 60%. HCA-SX was detectablein urine, and therefore its concentration could be used to determinerelative HCA absorption.

As discussed above, serotonin affects eating behavior and body weight.Increased plasma levels of serotonin are associated with decreased foodintake, reduced weight gain and increased energy expenditure.Researchers have shown that HCA-SX increases the release andavailability of serotonin from rat brain cortical slices ex vivo, withoptimal concentrations at 300 micromolar, as compared to concentrationsof 10, 30, 100 and 1,000 micromolar, indicating an optimal effectivedose of HCA-SX. Subsequently, human clinical studies have, for the firsttime, shown that effective doses of HCA-SX significantly increase serumserotonin levels. Because serotonin has been implicated in theregulation of eating behavior and body weight regulation, appetitesuppression induced by administration of HCA could be mediated by thisserotonin.

As discussed above, leptin is a biomarker for the gene that regulatesbody weight. Leptin is present in the bloodstream in amounts related tothe amount of fat in the body, and acts primarly on the brain toregulate food intake and energy expenditure. Leptin levels are higher inoverweight than in non-overweight individuals. Recently, human clinicalstudies have, for the first time, shown that effective doses of HCA-SXsignificantly reduce serum leptin levels and, thus, may down-regulatethe genetic propensity of a person toward obesity.

As discussed above, a possible mechanism of action may be HCA's abilityto increase fat oxidation. Enhanced oxidation of fat, including adiposetissue and triglycerides, is the primary source of the fat metabolitesmalondialdehyde, formaldehyde, acetaldehyde and acetone. Recently, humanclinical studies have shown that effective doses of HCA-SX significantlyincrease fat oxidation as determined by increases in urinary metabolitesmalondialdehyde, formaldehyde, acetaldehyde and acetone, and thus mayincrease fat degradation or “burning.”

Another dietary supplement known for use in regulating appetite andmodifying body composition is chromium. Chromium is an essential traceelement required for normal protein, fat and carbohydrate metabolism.Chromium levels are known to decrease with age, and marginal chromiumdeficiencies appear to be widespread. Chromium is important for energyproduction and plays a role in regulating appetite, reducing sugarcravings and increasing lean body mass. Chromium helps insulinmetabolize fat, turn protein into muscle and convert sugar into energy.Chromium has been shown to reduce levels of harmful LDL cholesterol, aform of cholesterol linked to heart disease, and increase levels ofbeneficial HDL cholesterol. Dietary trends that show increasedconsumption of more highly processed foods may lead to deficiencies ofchromium in persons.

Chromium potentiates the action of insulin in vitro and in vivo. Maximalin vitro activity of chromium requires a special chemical form termedGlucose Tolerance Factor (GTF). GTF is a chromium-nicotinic acid (i.e.,niacin) complex and is described in, for example, U.S. Pat. Nos.4,923,855, 4,954,492 and 5,194,615, all to Jensen and hereinincorporated by reference. Chromium extracted from Brewers yeast, whichis in the GTF form, is absorbed better than inorganic chromium. GTF istransported across the placental barrier, has different tissuedistribution from that of inorganic chromium, and has access to the bodypool of chromium that responds to increases in blood insulin. Thebiologically active form of chromium (GTF) is an essential dietary agentthat potentiates the action of insulin and thereby functions inregulating protein, fat and carbohydrate metabolism.

A particular form of GTF chromium, marketed under the name ChromeMate®by InterHealth Nutraceuticals, is a unique form of niacin-bound chromium(called chromium nicotinate or polynicotinate) that dramaticallyincreases the effectiveness of chromium in the effects discussed above.Normally, chromium is poorly absorbed and utilized by the body. However,researchers have found that the most potent form of chromium in nature(i.e., the form that best activates insulin) is bound to the B vitaminniacin. In particular researchers have found that a patentedoxygen-coordinated chromium-niacin complex is the most potent form ofall, being over 18-times more potent than the next closest form ofniacin-bound chromium tested. This oxygen-coordinated complex ischaracterized by chromium bound to an oxygen atom of the carboxylic acidgroup attached to niacin's pyridine ring structure.

As discussed above, chromium has been shown to reduce LDL cholesterollevels. In particular, administration of this oxygen-coordinatedniacin-bound chromium complex (also designated O-NBC) in sufficientamounts has been shown to reduce LDL cholesterol in humans by an averageof 14%. Researchers also have shown that O-NBC is significantly morebioavailable than chromium picolinate and chromium chloride.Supplementation with O-NBC therefore has been shown to ameliorate typeII diabetes, reduce hypertension, decrease fat mass, and increase leanbody mass, as well as help reduce body weight in persons consumingO-NBC. Additionally, high doses of O-NBC have been shown to becompletely safe and non-toxic. In contrast, chromium picolinate has beenshown to damage DNA and be mutagenic.

Previous studies also have shown the effectiveness of O-NBC in promotingweight loss. In a prior study, young obese women consuming 400micrograms of chromium as O-NBC per day, in combination with exercise,experienced significant weight loss over an eight-week study period. Incontrast, no change in weight was observed in subjects who exercised andconsumed chromium in the form of chromium picolinate or a placebo. Also,subjects who consumed chromium picolinate and did not exerciseexperienced significant weight gain during the study period. In anotherstudy, overweight African-American women consuming 600 mcg of chromiumdaily as O-NBC for 8 weeks had a significant loss of body fat andsparing of muscle compared with a prior placebo period of the sameduration. Increased fat loss also was observed among women who wererandomized to consume O-NBC first, followed by placebo, suggesting acarry-over effect of the supplementation on fat loss. No adverse effectswere observed from ingestion of O-NBC on the women in these studies.

Other known dietary supplements include plants in the genus Gymnema,such as Gymnema sylvestre, a traditional Ayurvedic herb known to balanceelevated blood sugar levels. The active ingredients in Gymnemasylvestre, gymnemic acid and gurmarin, have molecular structures similarto that to glucose and possess a number of health benefits. Gurmarin hasthe ability to fill taste bud receptors and reduce the sweet taste ofsugary foods, thus greatly reducing the craving for sweets. Gymnemicacid helps increase the production of insulin by stimulating theproduction of new insulin-producing cells, called beta-cells, in thepancreas. Gymnemic acid also facilitates insulin release from thebeta-cells into the blood stream by increasing beta-cell membranepermeability. Gymnemic acid also inhibits the absorption of sugarmolecules in the intestines during digestion, thus reducing increases inblood sugar levels. Finally, consumption of Gymnema sylvestre also hasbeen shown to significantly lower cholesterol in animal models.

Each of the materials described above are known to exhibit weightcontrol and/or other health promoting properties in persons or othermammals consuming them. However, individually, none provide all of theweight control and health promoting properties described above. It isapparent from the above that a need exists for improved methods andcompositions for controlling body weight and improving the healthcondition of persons or other mammals prone to excess body weight,including improvement of body mass index (an indicator of healthy bodyweight), serum leptin levels, serum serotonin levels, and thecardiovascular risk factors total cholesterol, LDL cholesterol, HDLcholesterol and triglycerides. The present invention fulfills this needand provides further related advantages.

SUMMARY OF THE INVENTION

The present invention resides in a composition comprising hydroxycitricacid, chromium, and gymnemic acid. In preferred aspects of theinvention, the hydroxycitric acid is bound to calcium and potassium. Thehydroxycitric acid in the composition preferably is derived from a plantof the genus Garcinia, most preferably Garcinia Cambogia. The chromiumin the composition preferably is niacin-bound chromium, and morepreferably oxygen-coordinated niacin-bound chromium. The gymnemic acidin the composition preferably is derived from a plant of the genusGymnema, most preferably Gymnema sylvestre. The composition may be inthe form of a pill, tablet, capsule, lozenge, gum, liquid, powder, food,beverage or other orally administered form.

The present invention also resides in related methods for increasingserotonin level, decreasing leptin level, or increasing fat oxidation ina person or other mammal, incorporating identifying a person or othermammal that can benefit from increased serotonin level, decreased leptinlevel and/or increased fat oxidation, and administering to the person orother mammal a composition comprising hydroxycitric acid in an amountsufficient to provide the required effect. Preferred aspects of themethod incorporate administration of hydroxycitric acid in forms asdescribed above. The method preferably incorporates administeringapproximately 100 milligrams to approximately 5,000 milligrams ofhydroxycitric acid daily, and more preferably approximately 2,700milligrams to approximately 2,800 milligrams. In the method, thecomposition preferably is administered daily in three substantiallyequally divided doses, approximately 30 to 60 minutes before meals,preferably orally. In preferred aspects of the method, the compositionalso incorporates chromium and gymnemic acid in forms as describedabove. Preferably, the method incorporates administering approximately10 micrograms to approximately 1,000 micrograms of chromium andapproximately 10 milligrams to approximately 1,000 milligrams ofgymnemic acid daily, and more preferably approximately 400 micrograms ofchromium and approximately 100 milligrams of gymnemic acid daily.

The present invention also resides in related methods for providing thefollowing effects in a person or other mammal: reducing excess, ormaintaining healthy, body weight or body mass index; decreasing appetiteand reducing food intake; and/or decreasing total cholesterol, LDLcholesterol and/or triglyceride levels, and/or increasing HDLcholesterol levels. The methods incorporate identifying a person orother mammal suffering, or at risk for suffering, from excess bodyweight, excess body mass index, elevated total cholesterol level,elevated LDL cholesterol level, elevated triglyceride level and/orreduced HDL cholesterol level; and administering to the person or othermammal a composition incorporating hydroxycitric acid, chromium andgymnemic acid in an amount sufficient to provide the required effect.The hydroxycitric acid, chromium and gymnemic acid preferably are in theforms described above. Preferably, the composition administeredincorporates approximately 100 milligrams to approximately 5,000milligrams of hydroxycitric acid, approximately 10 micrograms toapproximately 1,000 micrograms of chromium, and approximately 10milligrams to approximately 1,000 milligrams of gymnemic acid daily, andmore preferably approximately 2,700 milligrams to approximately 2,800milligrams of hydroxycitric acid, approximately 400 micrograms ofchromium, and approximately 100 milligrams of gymnemic acid daily.Preferably, the method incorporates administering the composition dailyin three substantially equally divided doses, approximately 30 to 60minutes before meals, preferably orally.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention resides compositions incorporating(−)-hydroxycitric acid (HCA), chromium and gymnemic acid. The presentinvention also resides in methods for controlling body weight andimproving the above-discussed health factors of persons or othermammals, including increasing serum serotonin levels, reducing serumleptin levels, increasing fat oxidation, reducing food intake, loweringbody mass index (BMI), and improving cardiovascular risk factors bydecreasing elevated total and LDL cholesterol, increasing HDLcholesterol and reducing elevated triglyceride levels. The methodsinclude identifying a person or other mammal who is, or is at risk forbeing, overweight, or who would benefit from the above-describedphysiological changes, and administering to the person or other mammal acomposition comprising sufficient amounts to effect the changes. Thepresent invention also resides in a composition which, when administeredto a person or other mammal, provides for the above-describedpsychological changes, the composition comprising a salt of HCA andother selected components.

The HCA used in the compositions preferably is in a form incorporatingboth calcium and potassium, to provide for superior solubility,bioavailability, and commercial utility. In preferred methods of thepresent invention, the composition administered also incorporates:chromium, preferably from oxygen-coordinated niacin-bound chromium, andGymnema sylvestre extract, providing gymnemic acid and gurmarin.Preferably, the method involves administering a compositionincorporating approximately 100 to 5,000 milligrams, and more preferably2,700 to 2,800 milligrams, of HCA daily to a person or other mammal whowould benefit from the physiological changes discussed above. Thepreferred composition to be administered also can incorporateapproximately 10 to 1,000 micrograms, and most preferably 400micrograms, of elemental chromium daily, preferably fromoxygen-coordinated niacin-bound chromium, and approximately 10 to 1,000milligrams, and most preferably 400 milligrams, Gymnema sylvestreextract providing approximately 5 to 500 milligrams, and most preferably100 milligrams, of gymnemic acid daily.

The methods of the present invention provide for the safe, effective andconvenient reduction of excess body weight and resulting reduction inbody mass index (BMI), or maintenance of healthy body weight and healthyBMI, in persons or other mammals. Besides these effects, administrationof the compositions also provides for reducing serum leptin levels,increasing serum serotonin levels, reducing food intake, increasing fatoxidation, decreasing elevated total and LDL cholesterol, increasing HDLcholesterol, and reducing elevated triglyceride levels in persons orother mammals that would benefit from such effects.

It has been surprisingly found that compositions incorporating thecomponents discussed above increase serum serotonin levels, reduce serumleptin levels and increase fat oxidation. It has also been surprisinglyfound that optimal concentrations of HCA exist for maximizing serumserotonin levels, a possible mechanism for decreasing appetite andreducing food intake. Another surprising finding is that compositionsincorporating the components described above provide for superiorimprovement in reducing excess body weight and improving the relatedhealth factors described herein than was expected based on thepreviously know properties of the components. Specifically, thecombination of HCA, chromium and gymnemic acid was shown to reduce bodyweight, lower body mass index, increase serum serotonin levels, reducefood intake, reduce serum leptin levels, increase fat oxidation,decrease harmful total and LDL cholesterol, increase beneficial HDLcholesterol and lower triglycerides significantly greater than HCAalone.

Preferred administration of the composition is orally, in threeequally-divided doses roughly 30 to 60 minutes before meals administereddaily. The composition also can include inert ingredients or diluents,such as sugar, maltodextrin, cellulose, or other inert ingredientscommonly used in food and beverage products. The composition may be invarious forms commonly used for dietary supplements, including pill,tablet, capsule, lozenge, gum, food, liquid, or powder. The compositionalso can be incorporated into food or beverage products, including bars,shakes, gums, beverages, or other processed or prepared food or beverageproducts, or any other orally administerable form.

Use of the methods and compositions of the present invention isillustrated in the Example below.

EXAMPLE

The effects of administering compositions within the scope of themethods of the present invention were tested. A double-blind,placebo-controlled human clinical trial was conducted using acomposition incorporating: the HCA-SX extract described above (SuperCitriMax™, supplied by InterHealth Nutraceuticals of Benicia, Calif.);and HCA-SX extract in combination with chromium (ChromeMate®, suppliedby InterHealth), and Gymnema sylvestre extract (also supplied byInterHealth).

82 moderately obese human subjects completed the study. All subjectswere placed on a daily diet of 2,000 kcal. All food was prepared anddelivered to the subjects, and all food intake was strictly supervisedby trained dieticians. All subjects also underwent a 30 minute walkingexercise program, five times a week, which was supervised by a trainedexercise specialist. The subjects were randomly divided into threegroups. The subjects in the first group were given a placebo. Thesubjects in the second group was given a daily dose of 4,667 mg ofGarcinia cambogia extract (providing 2,800 mg HCA per day). The subjectsin the third group were given a daily dose of 4,667 mg of a combinationof Garcinia cambogia (2,800 mg HCA), 4 mg of niacin-bound chromium(providing 400 mcg of elemental chromium), and 400 mg of Gymnemasylvestre extract (providing 100 mg gymnemic acid). The subjectsreceived their respective compositions in three equally-divided doses 30to 60 minutes before breakfast, lunch and dinner for eight weeks. Thesedosage levels of HCA were determined by extrapolation of successfulearlier animal trials, as well as review of optimal micromolarconcentrations of HCA in ex vivo brain tissue resulting in maximumserotonin release. Changes in body weight, lipid profile (triglycerides,LDL, HDL and total cholesterol), obesity gene level (determined by serumleptin level), serum serotonin levels, body mass index, fat metabolites(urinary malondialdehyde, formaldehyde, acetaldehyde and acetone levels)and appetite control were assessed in the persons. These changes wereaveraged to produce figures for analysis.

Results

Results of the testing are shown in Table 1 below. TABLE 1 Results ofAdministration of Compositions HCA-SX + chromium + Tested Factor PlaceboHCA-SX gymnemic acid Body Weight Pounds 3.5 10.0 12.8 % change 1.9 5.06.5 LDL Cholesterol mg/dl 3.0 −14.5 −22.6 % change 2.8 −13.0 −19.0 HDLCholesterol mg/dl −0.7 2.7 6.2 % change −2.7 9.0 21.4 Total Cholesterolmg/dl 1.1 −12.4 −16.6 % change 1.0 −7.4 −9.7 Triglycerides mg/dl 0.3−12.9 −22.6 % change 0.3 −10.0 −19.0 Serum Leptin Level ng/ml 0.4 −12.2−15.4 % change 1.0 −40.0 −42.6 Serum Serotonin Level mg/dl 20.1 119.1149.3 % change 10.9 48.5 70.4 Body Mass Index kg/m² −0.7 −2.4 −3.2 %change −2.0 −7.0 −9.2 Excreted Fat Metabolites % change Acetone 3.5 36.242.8 Formaldehyde 8.8 68.1 52.7 Malonaldehyde 12.6 60.6 65.3Acetaldehyde 18.1 64.4 73.0 Food Intake Reduction grams per day(average) 0 257 386.2 % change 0 11.4 17.2Discussion

The data from the study show that administration of the specified levelsof HCA extract results in: significant weight loss; decreases in bodymass index (an index of obesity health risk); reductions intriglycerides, LDL and total cholesterol (cardiovascular risk factors);increases in beneficial HDL cholesterol; increases in excretion of fatmetabolites (indicating increased fat oxidation or “burning”); decreasesin serum leptin levels (a biomarker of the obesity gene); increases inserum serotonin levels (a mechanism of appetite control and eatingbehavior); and, reductions in food intake. Further, the compositionincorporating all three components (HCA-SX, chromium and gymnemic acid)resulted in even greater improvement in all of the tested factors thanuse of the composition incorporating HCA-SX alone.

A number of interesting findings are observed from the results presentedabove. The constituents of the compositions demonstrated multifacetedactivities, which collectively resulted in a number of health benefits.Also, none of the constituents activated the central nervous system,demonstrating the relative safety of the compositions over, for example,ephedra-containing weight management formulas. HCA-SX exhibited itspredominant effect on the biochemical regulation of leptin, which is anintegral key component of obesity regulatory genes. Serotonin level alsowas modulated by HCA-SX alone, but it was more effectively modulated bythe combination of HCA-SX, chromium, and gymnemic acid. The effect ofserotonin level modulation was reflected in the reduced appetite in thestudy subjects.

An examination of the lipid profile data clearly shows that HCA-SX alonelowers LDL and triglyceride levels and increases HDL levels, however,the combination of HCA, chromium and gymnemic acid exhibited evengreater changes in these key components. Also, a high correlation existsbetween increased fat oxidation and enhanced excretion of urinary lipidmetabolites with a dramatic reduction in the triglyceride level.Glycerol is a product of the metabolism of triglycerides by adiposetissue and other brown tissues that possess a high glycerol kinaselevel. Glycerol kinase can activate the breakdown of triglycerides toglycerol, leading to enhanced formation of formaldehyde via microsomalmetabolism. This indicates that the compositions of the presentinvention can provide for enhanced biochemical induction of glycerolkinase, which can serve to enhance two important biochemical functions:biochemical reduction of triglyceride levels, and fat oxidation.

Although the invention has been disclosed in detail with reference onlyto the preferred embodiments, those skilled in the art will appreciatethat additional methods and compositions can be made without departingfrom the scope of the invention.

1-9. (Canceled)
 10. A method for increasing serotonin level in a personor other mammal comprising: identifying a person or other mammal thatcan benefit from increased serotonin level; and administering to theperson or other mammal a composition comprising hydroxycitric acid in anamount sufficient to increase serotonin level in the person or othermammal.
 11. A method as defined in claim 10, wherein the compositioncomprises hydroxycitric acid bound to calcium and potassium.
 12. Amethod as defined in claim 10, wherein the composition compriseshydroxycitric acid is derived from a plant of the genus Garcinia.
 13. Amethod as defined in claim 12, wherein the plant is Garcinia cambogia.14. A method as defined in claim 10, wherein the step of administeringcomprises administering approximately 100 milligrams to approximately5,000 milligrams of hydroxycitric acid daily.
 15. A method as defined inclaim 14, wherein the step of administering comprises administeringapproximately 2,700 milligrams to approximately 2,800 milligrams ofhydroxycitric acid daily.
 16. A method as defined in claim 10, whereinthe step of administering comprises administering the composition dailyin three substantially equally divided doses, approximately 30 to 60minutes before meals.
 17. A method as defined is claim 10, wherein thestep of administering comprises administering the composition orally.18. A method as defined in claim 10, wherein the composition furthercomprises chromium and gymnemic acid.
 19. A method as defined in claim18, wherein the composition comprises niacin-bound chromium.
 20. Amethod as defined in claim 19, wherein the composition comprisesoxygen-coordinated niacin-bound chromium.
 21. A method as defined inclaim 18, wherein the composition comprises gymnemic acid derived from aplant of the genus Gymnema.
 22. A method as defined in claim 21, whereinthe plant is Gymnema sylvestre.
 23. A method as defined in claim 18,wherein the step of administering comprises administering approximately10 micrograms to approximately 1,000 micrograms of chromium andapproximately 10 milligrams to approximately 1,000 milligrams ofgymnemic acid daily.
 24. A method as defined in claim 23, wherein thestep of administering comprises administering approximately 400micrograms of chromium and approximately 100 milligrams of gymnemic aciddaily. 25-102. (Cancelled)